Exploring The Evolution Process And Requirements For Molecular Recognition Via Highly Functionalized Aptamers

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dc.contributor.advisorHili, Ryan
dc.contributor.authorMovahedi, Matina
dc.date.accessioned2025-04-10T10:44:07Z
dc.date.available2025-04-10T10:44:07Z
dc.date.copyright2024-09-25
dc.date.issued2025-04-10
dc.date.updated2025-04-10T10:44:07Z
dc.degree.disciplineChemistry
dc.degree.levelDoctoral
dc.degree.namePhD - Doctor of Philosophy
dc.description.abstractExpanding the chemical diversity of oligonucleotide libraries has allowed the evolution of synthetic nucleic acid polymers with enhanced molecular recognition and catalytic abilities. Thus, synthetic methods that enable the sequence-defined incorporation of diverse chemical modifications in developing novel or improved nucleic acid polymers and selection methods that facilitate efficient enrichment of high-quality aptamers are of particular importance in identifying novel or improved nucleic acid polymers for diagnostics and therapeutics. In this thesis, the advancement of ligase-catalyzed oligonucleotide polymerization (LOOPER) is discussed as a method to increase the chemical diversity of oligonucleotide libraries and its application towards the evolution of modified aptamers. An evaluation of the use of different ligases, scope and number of modifications, sequence space, and evolutionary outcomes from in vitro selections is provided, along with a critical lens on challenges to be addressed for the method to mature into a more widely adapted technology. Further to this, a variety of selection methods are discussed striving towards efficient single-round aptamer selection. The successful single-round aptamer selection against Thrombin is an inspiring outcome for future selections.
dc.identifier.urihttps://hdl.handle.net/10315/42765
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subject.keywordsOligonucleotide therapeutics
dc.subject.keywordsAptamer
dc.subject.keywordsLOOPER
dc.subject.keywordsSELEX
dc.subject.keywordsCE
dc.subject.keywordsSingle-round selections
dc.subject.keywordsBLI
dc.subject.keywordsFP
dc.subject.keywordsBinding kinetics
dc.subject.keywordsHPLC
dc.subject.keywordsLCMS
dc.subject.keywordsDNA
dc.subject.keywordsRNA
dc.subject.keywordsm6A
dc.subject.keywordsHMDA
dc.subject.keywordsMolecular interactions
dc.subject.keywordsCatalysis
dc.subject.keywordsHighly modified functional oligonucleotides
dc.subject.keywordsG-quadruplex
dc.subject.keywordsLigation
dc.subject.keywordsFidelity
dc.subject.keywordsAmide coupling
dc.titleExploring The Evolution Process And Requirements For Molecular Recognition Via Highly Functionalized Aptamers
dc.typeElectronic Thesis or Dissertation

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